National Medical Research Center Research Articles

СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ ЛЕЧЕБНОГО ПИТАНИЯ ПАЦИЕНТОВ С ДЕТСКИМ ЦЕРЕБРАЛЬНЫМ ПАРАЛИЧОМ ПРИ НАРУШЕНИЯХ НУТРИТИВНОГО СТАТУСА

With the purpose of successful rehabilitation, reduction of concomitant diseases, improvement of nutritional status and the quality of life of patients with cerebral palsy (CP) it is necessary to develop therapeutic nutrition technology, which would include methods for nutritional status assessment, choosing of enteral nutrition formulas, methods of their delivery and the duration of nutritional support. The purpose of this research was to substantiate the nutritional support for patients with CP. Materials and methods used: 98 children aged 2 to 16 years and 9 months old (Me 5.7 y/o) with a spastic form of CP that had been admitted for examination, treatment and rehabilitation at the National Medical Research Center for Children’s Health (Moscow, Russia) were examined. Depending on the level of motor activity calculated with GMFCS, the participants were divided into two groups: G1 of 51 (52%) with severe motor impairment (GMFCS IV to V) and G2 of 47 (48%) with mild and moderate motor impairment (GMFCS I to III). Clinical and anamnestic data, information about the severity and the course of the disease, concomitant pathology were analyzed as well as the anthropometric data (Z-scores: weight/age, height/age, BMI/age) using the WHO AnthroPlus application (2009 revision). EDACS survey had also been carried out. Results: Patients with severe motor impairments were significantly more likely to have problems associated with food intake, such as: prolonged feeding (over 30 minutes), predominance of semi-liquid and pureed food in the diet as well as frequent choking, vomiting, wheezing and coughing during the feeding process. All patients in this group needed external assistance in feeding. 75% had respiratory and 72% had gastrointestinal complications. Severe impairments (EDACS IV to V) characterized by significant restrictions on food safety were identified in 24 (23%) children, that met statistically significantly (p<0.001) more often in patients from G1 than from G2 (41% vs. 4%, respectively). Dietary analysis children with CP had showed that the quality and quantity of food consumed were monotonous and deficient. Consumption of pasta, cereals, and baking was 1.5 times higher than recommended whilst vegetables, fruits and healthy dairy products were reduced by 3 and 1.8 times, respectively, on the contrary. The WHO recommendations for children on the mandatory daily intake of 3 to 4 servings of various vegetables and fruits were not followed: in the majority (80%) of cases they’ve only had it once per day, and they even were completely absent in some cases. Nutritional assessment revealed that patients with severe movement disorders, regardless of the gender and nutritional status, had significant deficiencies in energy and protein intake. All studied anthropometric indicators in G1 patients were significantly (p<0.005) lower compared to G2 children. Prevalence of undernutrition was 72% and 32% (p<0.001), respectively. Individual nutritional program was developed for each and every studied patient with identified malnutrition and oropharyngeal dysphagia, followed by its clinical effectiveness assessment. Conclusion: enteral nutritional support with specialized formulas based on both whole and hydrolyzed proteins using the sipping/gastrostomy method, as well as with the use of a food and liquids thickeners, proved to be highly effective in the treatment and rehabilitation of CP children. Indicators characterizing food intake (time taken for feeding, frequency of choking records during meals, episodes of vomiting and regurgitation) have improved as well as the anthropometric indicators improved accordingly.

Clinical experience of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus

Introduction. Laryngopharyngeal cancer accounts for about half of the total number of malignant neoplasms of ENT organs. Despite the availability of examination, in most patients tumors of this localization are detected at late stages, and the long-term results of treatment of locally advanced cancer of the larynx remain unsatisfactory.Clinical case. This article presents two clinical cases of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus. At the first stage, patients underwent organ-preserving surgical treatment with a reconstructive plastic component according to the methodology developed at the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Center of Radiology. Then a postoperative course of chemoradiotherapy was carried out.Conclusion. The use of combined organ-preserving techniques using displaced skin-muscle flaps in the treatment of locally advanced laryngopharyngeal cancer involving the cervical esophagus allows in some cases to avoid crippling surgery, preserve the larynx and achieve satisfactory functional results, which significantly improves the quality of life of patients.

Endoscopic criteria for early differential diagnosis of gastritis-like form of primary non-Hodgkin's lymphomas and gastric cancer: A prospective study

Aim. To reveal and study basic endoscopic differential-significant criteria characterizing gastric-like form of primary non-Hodgkin's lymphoma (NHL) from adenocarcinoma and signet-ring cell carcinoma (SRCC) of the stomach.
 Materials and methods. In the prospective study, based of Blokhin National Medical Research Center of Oncology in the period from 2019 to June 2023, 106 patients with gastritic-like forms of primary NHL, adenocarcinoma and SRCC of the stomach were analyzed. Complex endoscopic study included examination in the modes of white light, magnification, narrow-band imaging (NBI, BLI, LCI) was done.
 Results. All patients were divided into three groups: MALT gastric lymphoma (38 patients, 35.8%), gastric adenocarcinoma (33 patients, 31.1%), and SRCC (35 patients, 33.1%). At MALT-lymphoma the tumor was localized in the antrum of the stomach (52.6%),adenocarcinoma and SRCC – in the body (45.5 and 60%). In the tumor structure in MALT-lymphoma of the stomach in 100% of cases multiple point areas of microdepressions and multicenter character of the lesion were determined. At adenocarcinoma – depressed area in the central part of tumor (45.5%), at SRCC – extended areas of microdepressions (51.4%) and multicentric character of lesions. At MALT-lymphoma the pit pattern in 63.2% is of "balloon" type, vascular – of tree-like type (84.2%). In adenocarcinoma the vascular pattern was of the loop-type (42.4%), in SRCC – of the corkscrew-type (74.3%). Demarcation line was observed only in adenocarcinoma (100%). At endosonographic study at MALT-lymphoma the tumor was coming from deep layers of mucous coat (100%), changes of regional lymph nodes (LN) were absent, at adenocarcinoma – from mucous membrane (100%), LN were not changed, at SRCC – submucous spread of tumor (100%), changes in LN (40%).
 Conclusion. Complex endoscopic examination is necessary to improve the quality of endoscopic examination of malignant gastric-like tumors, to determine the depth of invasion and spread of the tumor process, to assess the regional lymph drainage.

Validation of genetic risk scores for type 2 diabetes on a Russian population sample from the biobank of the National Medical Research Center for Therapy and Preventive Medicine

Aim. To validate and evaluate the accuracy of 14 genetic risk scores (GRSs) for type 2 diabetes (T2D), created earlier in other countries, using a Russian population sample from the biobank of the National Medical Research Center for Therapy and Preventive Medicine.Material and methods. For genetic analysis, next generation sequencing data was used on a sample from the Russian population (n=1165) based on the biobank collection. The study included 14 GRSs associated with T2D.Results. The study demonstrated that the predictive power of 12 out of 14 GRSs for T2D was replicated in the Russian population. As quality metrics, we used the area under the ROC curve, which for models including only GRS varied from 54,49 to 59,46%, and for models including GRS, sex and age — from 77,56 to 78,75%.Conclusion. For the first time in Russia, a study of 14 T2D GRSs developed on other populations was conducted. Twelve GRSs have been validated and can be used in the future to improve risk prediction and prevention of T2D in Russia.

Relationship of the integrin profile of the primary tumor to metastasis to regional lymph nodes in breast cancer

Background. Breast cancer ranks first in the structure of cancer morbidity and mortality. Involvement of a large number of regional lymph nodes is considered a poor prognostic outcome. The mechanisms of development of lymphogenous metastasis in general and common in particular are not fully understood. Integrins are involved in the metastatic process by mediating tumor cell invasion and adhesion to vascular endothelium.
 Aim. To study the role of integrins in lymphogenous metastasis.
 Materials and methods. The study included 72 patients diagnosed with invasive breast carcinoma of no special type who underwent surgical treatment on the basis of the cancer research institute national research medical center. The average age reached 51.2 years. In accordance with the indications and morphological data, the patients underwent antitumor treatment. The tissue of the primary tumor obtained by trepanbiopsy. Histological and immunohistochemical examination was carried out according to the standard method. In primary tumor cells, the presence or absence of cytoplasmic or membrane/cytoplasmic colocalization of CD61 (Integrin beta 3), CD104 (Integrin beta 4), CD51 (Integrin alpha-V) expression was assessed. When statistically processing the results, Fisher's test and one-way regression analysis were used.
 Results. In the N3 group, the frequency of cytoplasmic expression of CD 61 was higher at the trend level (40.9 and 18%; p=0.074). In the group of patients with N3, positive cytoplasmic expression of CD104 (37.5 and 15.0%; p=0.029) and membrane and cytoplasmic colocalization (52.6 and 15.1%; p=0.004) were more often detected. In the group with N1 and N2, membrane and cytoplasmic colocalization of CD104 expression was less common (15.8 and 54.7%; p=0.006). When studying the expression frequency of CD51 integrin, no significant differences were found depending on the severity of lymphogenous metastasis.
 Conclusion. Expression of CD104 in primary tumor cells is strongly associated with widespread lymphogenous metastasis. Studies of the role of integrins in the development of lymphogenous metastasis are promising for predicting the prevalence of this process in the preoperative period and for searching for methods of influencing the tumor.

Epidemiology of pain in spinal cord injury

BACKGROUND: The original Pain syndrome in spinal cord injury, which by its nature is one of the most severe and debilitating conditions, can lead to a deterioration in the quality of life, depression, sleep disorders and, as a consequence, a decrease in the results of rehabilitation treatment. This article will present epidemiological data of pain syndrome in spinal cord injury.
 AIM: To study the structure and features of pain syndrome in patients with spinal cord injury.
 MATERIALS AND METHODS: The clinical data on a sample of patients with pain syndrome in spinal cord injury are analyzed (n = 75). The study group was represented by male patients (100%), whose average age was 36 years, undergoing inpatient treatment on the basis of the National Medical Research Center for High Medical Technologies — A.A. Vishnevsky Central Military Clinical Hospital, Ministry of Defense, Russia. The analysis of pain syndrome in this cohort was carried out on 8 indicators at once: neurological level of injury, localization of pain, intensity of pain, motor neurological deficit, degree of damage to the anatomical integrity of the spinal cord, the presence of a neuropathic component, the type of pain syndrome and characteristic pain descriptors.
 RESULTS: According to the classification of pain in spinal cord injury, proposed by an international consensus of clinicians and researchers, the prevalence of various types of pain among the study group was presented as follows: neuropathic — 64%, nociceptive — 32, dysfunctional — 4%. Analyzing various subtypes of neuropathic pain, pain below the injury level dominated — 72%.
 CONCLUSION: The most common and difficult to stop variant in the structure of pain syndrome in patients with spinal cord injury is neuropathic pain.

Bioresource collections: algorithms for development and functioning; basic and applied significance

Bioresource collection of the N. N. Blokhin National Medical Research Center of Oncology is a unique structured biobank that combines different types of primary and subsidiary samples and ensures its comprehensive characterization, including both generally accepted indicators and specific types of research. Samples of paraffin blocks, frozen material, blood and its derivatives are deposited in the clinical department of the center. The research institute of the center has collected commercial and unique human cell lines and transplantable strains obtained from clinical material, as well as cells from laboratory animals, mainly of mouse origin. The provided cell lines undergo multi- stage quality control, including confirmation of authenticity, assessment of viability and determination of optimal cultivation conditions, analysis of interspecific and intraspecific contamination, study of tumorigenicity and reproducibility in athymic Balb/ c-nude mice, etc. In addition, the Bioresource Collection has hybridoma clones that produce antibodies to a wide range of targets. The Center provides the opportunity to conduct preclinical research using samples from the Bioresource Collection to obtain scientific and regulatory data on the antiproliferative activity of new agents or methods for cancer treatment.

Biobanking in the hospital of a multidisciplinary research medical center as a potential for a wide research range. Part I. Organizational and methodological aspects

Aim. To develop an algorithm and manage total biobanking of samples of whole blood, serum and plasma of patients in the hospital of the National Medical Research Center for Therapy and Preventive Medicine in order to create a detailed biosample collection through the integration of electronic medical records and a biobank database.Material and methods. The study includes all patients admitted to the hospital of the National Medical Research Center for Therapy and Preventive Medicine in various departments who signed informed consent for biobanking. Clinical information is collected as part of patient examination and stored in electronic medical records in the Medialog medical information system. Biobanking of blood and related products is carried out in accordance with standard operating procedures. From each patient, 12 aliquots of serum and blood plasma are stored, as well as 1 tube of whole blood with ethylenediaminetetraacetic acid potassium salt. Information about biospecimens, patient identification numbers and storage location coordinates are contained in the biobank database.Results. An algorithm for total biobanking of biomaterial and data from inpatients has been developed and put into practice. This collection is associated with large biomedical data stored in a medical information system, laboratory information system and biobank. The combined databases make it possible to search for samples in the collection according to specified criteria.Conclusion. The collection developed can be used for a wide range of studies by forming patient samples according to the necessary criteria. The developed algorithm for total biobanking in a hospital can be used in various medical centers equipped with biobanks.

Biobanking in the hospital of a multidisciplinary research medical center as a potential for a wide research range. Part II. Specifics and first results of developing a described collection of biomaterial

In connection with the development of genetic and other types of research in translational medicine, collections containing a significant number of biospecimens and large data sets are required. Since in-depth examination of patients is most often carried out during hospitalization, the creation of collections based on electronic medical records (EMR) data is promising. In this regard, the project "Total biobanking in the hospital of the National Medical Research Center for Therapy and Preventive Medicine" was initiated, aimed at total biobanking of blood and related products from patients in inpatient departments and the creation of a unified system that combines information on biosamples, clinical and other types of data.Aim. To describe the collection of biospecimens collected within the project "Total biobanking in the hospital of the National Medical Research Center for Therapy and Preventive Medicine" for August 2023, and to analyze the process of biospecimen description.Material and methods. Recruitment of patients is carried out on the basis of inpatient departments of the National Medical Research Center for Therapy and Preventive Medicine, only if the patient signs informed consent. After blood is taken, the biomaterial enters the biobank, where sample preparation and storage is carried out, as well as data about each biosample is entered into a special FreezerPRO system. At the same time, clinical data about the patient is collected using EMR, which are combined in the Medialog medical information system.Results. A special software for data exchange between the medical information system and the biobank has been developed, which combines information about patients entering the Medialog medical information system and the FreezerPro biospecimen management system, which contains detailed information about biospecimens. As of August 25, 2023, biomaterial from 3996 patients was collected, which was accompanied by a detailed clinical summary. In particular, data is available on diagnoses (for 100% of patients), laboratory test data (100%), paraclinical data, in particular, electrocardiography (100%), echocardiography (76,8%), 24-hour Holter monitoring (59,8%), esophagogastroduodenoscopy (27,3%), etc. The most common diseases were hypertension (76,0%), atherosclerosis (69,9%), coronary artery disease (52,9%), arrhythmias (50,6%), diabetes (19,2%). In addition, 25,0% of patients had prior stenting.Conclusion. Total biobanking within the hospital of a multidisciplinary research medical center allows for the rapid and high-quality collection of biomaterial and related data. A collection of biospecimens with comprehensive and detailed clinical annotations has been collected. A primary analysis of the collection was carried, which showed that it can be used for a wide range of studies.

Forms of interaction between the National Medical Research Center for Anesthesiology and Critical Care Medicine (for adults) and the regions of the Russian Federation

In order to implement the Federal Project “Development of a Network of National Medical Research Centers and Implementation of Innovative Medical Technologies”, the National Medical Research Center (NMRC) on the “Anesthesiology and Intensive Care (for adults)” was established in 2021 on the basis of the Sechenov First Moscow State Medical University (Sechenov University), designed to perform organizational and methodological management of specialized units of medical organizations of regions of the Russian Federation. Aim. Evaluate the contribution of Sechenov University to the implementation of the federal project “Development of a network of medical research centers and the introduction of innovative medical technologies” using the unique experience of the NMRC as an example.. Materials and methods. Analysis of the results of NMRC visits to the regions of the Russian Federation. Reports review of medical organizations of the regions of the Russian Federation. The involvement of medical personnel of the regions in the system of continuous medical education, including scientific and practical events carried out by NMRC, and the demand for the use of telemedical consultations were assessed. Results. During 17 months of the NMRC work 15 of on-site inspections in the regions of Russian Federation were carried out in order to analyze the level of anesthesiology and intensive care services in the regions of Russian Federation, 2577 telemedical consultations were provided, and 15 interactive educational modules for the portal of continuous medical and pharmaceutical education of Ministry of Health of Russia were prepared. Conclusion. The main forms of NMRC’s interaction with the regions of the Russian Federation are organizational and methodological, scientific and educational support of the representatives of healthcare practitioners and regional healthcare authorities. The NMRC activities are aimed at improving the quality of medical care in the field of anesthesiology and intensive care in the regions of the Russian Federation and the formation of a value-oriented approach in modern health care.

Medical and Socio-Pedagogical Risks of Primary School Children Using Digital Devices: An Empirical Study

The study considers the medical and socio-pedagogical risks of primary school children using digital devices and social networks, based on the results of a medical and social study, the purpose of which was to assess and systematize these risks. The digital devices, the Internet and activities on social networks have become an integral part of the lives of modern children. However, their use can negatively affect the neuropsychic status of the child and lead to problems with vision and the musculoskeletal system. For this reason, parental control over the use of gadgets and social networks that is safe for children’s health is very important. The methodological basis of the research was social pedagogy, which explores the processes of interaction of a growing person with various objects of society in the main spheres of his/her life: family, educational and social, performing an integrating function in the study of current social problems of children, families and society by various scientific disciplines. A complex of research methods was used, with the main one being a questionnaire survey of parents with children of primary school age and living in the Borovsky district of the Kaluga region (the research base of the Research Institute of Hygiene and Health Protection of Children and Adolescents, National Medical Research Center for Children’s Health of the Ministry of Health of the Russian Federation). It was found that watching videos is a risk of increased irritability, computer games, searching for information on the Internet, uncontrolled use of digital media - a risk of visual impairment, using social networks - complaints for communication difficulties. More than 50% of parents need help from specialists in improving digital literacy and using digital devices safely for children’s health.

Factors Associated With Hospital Mortality in Acute Myocardial Infarction

Aim To determine clinical and laboratory parameters associated with in-hospital mortality in patients with acute myocardial infarction and to develop a multifactorial prognostic model of in-hospital mortality.Material and methods This was a study based on the 2019-2020 Registry of acute coronary syndrome of the Tyumen Cardiology Research Center, a branch of the Tomsk National Research Medical Center. The study included 477 patients with ST-segment elevation acute myocardial infarction (AMI), 617 patients with non-ST segment elevation AMI, and 26 patients with unspecified AMI. In-hospital mortality was 6.0 % (n=67). Clinical and laboratory parameters were assessed on the day of admission. The separation power of indicators associated with in-hospital mortality was determined using a ROC analysis. The data array of each quantitative parameter was converted into a binary variable according to the obtained cut-off thresholds, followed by creation of a multifactorial model for predicting in-hospital mortality using a stepwise analysis with backward inclusion (Wald). The null hypothesis was rejected at p<0.05.Results The multivariate model for prediction of in-hospital mortality included age (cut-off, 72 years), OR 3.0 (95 % CI: 1.5-5.6); modified shock index (cut-off threshold, 0.87), OR 1.5 (95 % CI: 1.1-2.0); creatine phosphokinase-MB (cut-off threshold, 32.8 U / L), OR 4.1 (95 % CI: 2.2-7.7); hemoglobin (121.5 g / l), OR 1.7 (95 % CI: 1.2-2.3); leukocytes (11.5×109 / l), OR 1.9 (95 % CI: 1.3-2.6); glomerular filtration rate (60.9 ml / min), OR 1.7 (95 % CI: 1.2-2.2); left ventricular ejection fraction (42.5 %), OR 4.1 (95 % CI: 2.0-8.3); and size of myocardial asynergy (32.5 %), OR 2.6 (95 % CI: 1.4-5.0).Conclusions Independent predictors of in-hospital mortality in AMI are age, modified shock index, creatine phosphokinase-MB, peripheral blood leukocyte count, hemoglobin concentration, left ventricular ejection fraction, size of myocardial asynergy, and glomerular filtration rate. The in-hospital mortality model had a high predictive potential: AUC 0.930 (95 % CI: 0.905-0.954; p <0.001) with a cutoff threshold of 0.15; sensitivity 0.851, and specificity 0.850.

Desmin Degradation in the Skeletal Muscle of Patients with Chronic Critical Illness

Chronically critically ill patients lose a significant amount of muscle mass during their stay in the intensive care unit, which can have long-term detrimental consequences. This, among other factors, leads to the degradation of the muscle cytoskeleton’s integrity, and at present there are no comprehensive studies that describe the mechanisms b-ehind the development of this process. The purpose of this study was to investigate the signaling processes that contribute to the degradation of desmin in patients with critical illness myopathy (CIM). Incisional muscle biopsies were taken from the soleus muscle from 6 patients undergoing treatment at the A.L. Polenov Russian Research Institute - branch of the Almazov National Medical Research Center, with chronic impairment of consciousness (lasting at least 2 months). Muscle biopsies taken from healthy men using a needle biopsy technique were used as controls. Biopsies were frozen in liquid nitrogen for subsequent Western blot and PCR analysis, as well as immunohistochemical studies. The analysis showed that fibers with an altered histological pattern of desmin were visually identified in 4 out of 6 patients studied. We also observed a significant decrease in desmin content by 69% and a 24% decrease in its mRNA content in patients with CIM. Desmin breakdown may be associated with increased calpain activity and activation of the ubiquitin-proteasome system. In this study, the content of calpain-1 increased under conditions of CIM at the protein level, but remained unchanged at the mRNA level. We observed changes in GSK3-β (Ser9) phosphorylation, which is a crucial step in the d-epolymerization of desmin filaments by calpain-1. A study on ubiquitin ligases revealed a significant 155% increase in the expression of Trim32, along with a decrease in the e-xpression of Atrogin1 and MuRF1. Thus, in this study, we observed a decrease in desmin content under conditions of CIM. The breakdown of desmin may be due to increased phosphorylation by GSK3β and subsequent cleavage by calpain-1. In addition, we observed an increase in the expression of the E3 ubiquitin ligase Trim32, the activity of which, according to literature, also increases after phosphorylation of desmin.

Clinical application of new classification of the calyx-pelvic system dilation UTD in children in a perinatal center

The aim of the study was to evaluate the clinical significance of the new urinary tract dilation classification (UTD-2014) in predicting outcomes of the calyx-pelvic system dilation detected by ultrasound (US) in children in the perinatal center.Materials and methods. A retrospective analysis of the urinary system ultrasound protocols and the outcomes of 152 children with dilated calyx-pelvic system due to various causes examined at the National Medical Research Center for Obstetrics, Gynecology and Perinatology for the period from 2017 to 2022 was carried out.Results. The median age of patients at the time of the first ultrasound was 2 days, the median duration of follow -up was 10 months. The decrease in the UTD category during the observation period occurred in –/35/29/10% of patients in groups with the primary established UTD category 0/I/II/III, respectively. The UTD category remained the same in 42%, an increase in the category occurred in 32/26/4/-% of patients with UTD 0/I/II/III, respectively. The age at the time of the first ultrasound of patients who had an increase in the UTD category (median – 2 (1; 3.5) days) was significantly less than in other children (with the exception of operated patients). Surgical intervention was performed by 0/2/31/60% of patients with UTD category 0/I/II/III (only 18%), respectively.Conclusions. UTD classification correlates well with outcomes of the calyx-pelvic system dilation due to various causes in children – the larger the category according to primary ultrasound, the less often its decrease or lack of dynamics is noted during follow-up, surgical treatment is more often necessary. When using the UTD classification in the perinatal center, there is a high risk of underestimating the degree of dilatation due to the early conduct of the first ultrasound in the first two days of life.

Methotrexate-induced transient encephalopathy. The experience of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Introduction. Methotrexate is one of the main chemotherapeutic agents of group antimetabolits, includes in the first line of therapy against osteosarcoma. The drug uses in dose 12 g/m2 according to the protocol EURAMOS-1. The range of methotrexate-induced complications includes renal toxity, hepatotoxicity, myelosuppression, skin and mucosal ulcerations, dyspeptic disorders. One of the formidable, but reversible complications, is methotrexate-induced transient encephalopathy (MIE), the clinical manifestations of which occur in more than 15 % of patients in the treatment of which high doses of methotrexate (HD MTX) are used.Materials and methods. At the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia the period from 2013 to 2023 10 cases of MIE were recorded. All patients received therapy according to the protocol EURAMOS-1. The 4 out of 10 patients had a delay in the rate of elimination of HD MTX after the course of chemotherapy. No one patient had electrolyte disturbances with using HD MTX. The median occurrence of the complication’s emerging was 7 days (from 5 to 10 from the start of therapy) and most often developed after 3 courses of methotrexate 12 g/m2 , which corresponds in total 6 doses of methotrexate. Neurological symptoms: headache, visual impairment, aphasia, convulsions were transient and resolved after an average of 24 hours from the start of the treatment.Results. All 10 patients received obligatory alkalization, massive infusion therapy, neuroprotective drugs, as well as decongestant therapy as a treatment of MIE. Subsequently, therapy with methotrexate was continued for the 9 of 10 patients.Conclusions. The standard recommendations for the treatment of MIE do not currently exist. However, the development of severe neurotoxicity does not exclude the possibility of further using of HD MTX in the treatment program

Primary Ewing’s sarcoma of the kidney: description of two rare clinical cases and review of world literature

Ewing’s sarcoma (ES) of the kidney is an extremely rare malignant tumor characterized by an aggressive course, and therefore the disease has an unfavorable prognosis. Due to the rare occurrence, standards for the treatment of ES of the kidney have not been developed; an integrated approach is often used in therapy. In this article, we present a description of two clinical cases of kidney damage with ES in patients aged 10 and 16 who were treated at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. In the first case, there was a metastatic lesion of the kidney with the localization of the primary focus in the pelvic bones, in the second, primary ES of the kidney was diagnosed. Both patients had stage IVb at the time of diagnosis (TNM classification American Joint Commission on Cancer). In both patients, after induction chemotherapy, a complete therapeutic response (complete therapeutic pathomorphosis) was obtained. In an integrated approach, in addition to standard chemotherapy, surgery and radiation therapy, in both cases, high-dose chemotherapy with autologous peripheral stem cell transplantation was used, which made it possible to create favorable conditions for long-term remission in one of the patients, even despite the initial prevalence of the process.

Toxic complications of high doses of treîsulfan in children: experience of the N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia

Hematopoietic stem cell transplantation (HSCT) is a treatment method for a number of severe malignant and non-tumor diseases. Autologous (auto) and allogeneic (allo) HSCT improves outcomes in patients with solid and hematological malignancies. The toxicity of conditioning regimens before HSCT is often a limiting factor for successful transplant outcomes. The most common manifestations of visceral and tissue toxicity are epithelial (dermatological and mucosal) toxicity, hepatotoxicity, and neurotoxicity. Reducing the incidence of toxic complications of preparative regimens preceding HSCT is the optimization of accompanying therapy, and and individualized selection of doses of chemotherapy. In our study, among 119 HSCT cases performed in 2021–2022, treosulfan-containing preparative regimens were used. Dermatological toxicity was diagnosed in 80.0 %, mucositis – in 100 %, hepatotoxicity – in 18.5 % of observations, no neurological toxicity was recorded.

Effectiveness of Physiotherapy Methods in Medical Rehabilitation of Patients with Shoulder and Scapular Pain Syndrome in a Sanatorium: a Randomized Clinical Study

INTRODUCTION. The high prevalence of shoulder pain syndrome (SPS) determines the relevance of the development of new comprehensive methods of rehabilitation of this category of patients.
 AIM. To evaluate the clinical effectiveness of shockwave therapy (SWT) and pulsed low-frequency electrostatic field (PLEF) in patients with SPS undergoing medical rehabilitation in a sanatorium-resort organization in comparison with traditional health resort treatment.
 MATERIALS AND METHODS. The comparative analysis of medical rehabilitation efficiency was carried out in 90 patients with SPS aged 31–68 years undergoing medical rehabilitation in the health resort complex “Vulan” — a clinical branch of National Medical Research Center for Rehabilitation and Balneology. All patients were divided into 3 groups of 30 persons each by the method of simple randomization. Group 1 patients (control) received traditional health resort treatment, including ozokeritotherapy, physical exercise therapy, electrotherapy with sinusoidal modulated currents and manual massage. Patients of the second group (comparison) received against the background of the above complex 3 SWT procedures on the shoulder joint once a week. Group 3 patients (main group) received, in addition to traditional treatments, 3 SWT and 8 field PLEF treatments administered every other day. The effectiveness of rehabilitation was evaluated according to the severity of pain syndrome (VAS scale), Swanson’s scale for the shoulder. Movement volume before and after rehabilitation was measured with an orthopedic angle gauge. Microcirculation state was assessed by laser Doppler flowmetry (LDF). Leukert scale was used to assess the state of well-being. The results of the study were assessed 18 days after the beginning of rehabil itation measures.
 RESULTS AND DISCUSSION. Patients who additionally received SWT and PLEF against the background of traditional health resort treatment noted a significant reduction in the severity of pain syndrome, while in the main group pain regression was noted earlier (on day 4–5), whereas in the comparison group the same results were obtained by the day 14th . In the control group, patients noted significant changes on the VAS scale only by the end of the rehabilitation course. On the Swanson scale, the most significant positive results were also obtained by the patients in the main group: the pain decreased on average 2.6-fold, the volume of active movements in the shoulder joint increased 2.7-fold, and activity in everyday life 1.9-fold. Statistical differences in the Swanson Scale scores with the comparison group were obtained with regard to pain syndrome and volume of active movements. When comparing with the control group, reliable differences were revealed in all Swanson’s scale indicators in both the main group and the comparison group. When studying the dynamics of microcirculation according to LDF data, it was noted that reliable changes in the main indices of the LDF-gram were revealed only in the groups that received innovative physical therapy interventions.
 CONCLUSION. Thus, the inclusion of modern physiotherapeutic techniques of SWT and PLEF into the program of health resort treatment of patients with SPS allows to increase significantly the efficiency of medical rehabilitation carried out in the sanatorium organization.

Retrospective Analysis of Experimental and Clinical Studies of the Effect of Sodium Chloride Baths on the Body

AIM. Retrospective analysis of experimental and clinical studies of the effect of sodium chloride baths on the body.
 MATERIALS AND METHODS. The retrospective analysis included experimental and clinical studies revealing the mechanisms of action of sodium chloride baths on the human body, as well as their therapeutic effect in the rehabilitation of patients with various chronic non-communicable diseases, which were carried out on the basis of the National Medical Research Center for Rehabilitation and Balneology over the past 60 years.
 RESULTS. It was found that sodium chloride baths (HCV) have a distinctive, inherent effect for them, which depends on the concentration of sodium chloride, the temperature of the water in the bath and the initial state of the body. Experimental work has proved the different effect of HCV of different concentrations on the function of the adrenal cortex. It was found that with an increase in the concentration of sodium chloride in the bath, the observed changes were more pronounced. In the experiment, it was revealed that as a result of the action of HCV, general reactions of the whole organism were observed. Baths with a sodium chloride concentration of 30 g/l change the functional state of the brain in the direction of reducing excitability, and baths with a sodium chloride content of 60 g/l in the direction of its increase. It has been established that HCV is an adequate and pathogenetically justified method of treating patients with CKD. The realization of the therapeutic effect of baths was determined by their anti-inflammatory and desensitizing effect, influence on central and regional hemodynamics. Baths with a sodium chloride concentration of 40 g/l had a more pronounced positive effect. Studies conducted in patients with hypertension have proven the benefits of using HCV with a lower temperature of 31–32 °C. It is also proved that in patients of this category, the use of HCV with a concentration of 40 g/l had a more pronounced hypotensive, antianginal effect and led to an increase in physical performance, to an improvement in central, peripheral and cerebral hemodynamics compared with baths with a concentration of 20 g/l. Other studies testified to the beneficial effect of HCV in coronary heart disease, which was expressed in improving the contractile function of the myocardium and increasing the level of physical performance and coronary reserve of the heart. Analgesic, anti-inflammatory, desensitizing effect of HCV was noted in patients with degenerative-dystrophic and infectious nonspecific joint lesions.
 CONCLUSION. The presented scientific works of retrospective analysis reveal the mechanisms of the biological and therapeutic effects of HCV. The data obtained are the justification for their use in a number of diseases. For a more successful use of HCV, further regular generalization and analysis of existing evidence-based studies, as well as the implementation of new qualitative randomized controlled clinical trials of the action of HCV, first of all, the determination of the optimal concentration for each nosology, is necessary.

Analysis of treatment outcomes in patients with combat spinal column and spinal cord injuries

Introduction. Spinal column and spinal cord injuries are one of the most severe types of trauma. The paper presents the results of examination and treatment of 80 patients with combat spinal column and spinal cord injuries treated in the neurosurgical department of the FSBI National Medical Research Center for High Medical Technologies — A. A. Vishnevsky Central Military Clinical Hospital. Purpose. To analyze the structure of incoming wounded patients and the results of treatment of patients with combat spinal injury in the conditions of a multidisciplinary medical center. Materials and methods. The paper analyzes the results of treatment of 80 patients with combat spinal column and spinal cord injuries treated in the Neurosurgery Center, FSBI National Medical Research Center for High Medical Technologies — A. A. Vishnevsky Central Military Clinical Hospital. The inclusion criteria were the radiological signs of combat spinal injury upon admission to the hospital. Upon admission, all patients underwent pan CT scan, their somatic and neurological status was assessed, and laboratory parameters were evaluated. Gunshot wounds were found in 66.25 % (n=53) of the patients, and blunt combat injuries to the spine were found in 33.75 % (n=17). Concomitant injuries were sustained by 81.25 % (n=65) of the studied patients. Prior to admission to the Neurosurgery Center, neurosurgical care was provided to some of the wounded. Spinal surgery was performed in 30.0 % (n=24) of the cases, and 56.25 % (n=45) were operated on for injuries to other anatomical regions and organ systems. Results. 69 % (n=55) of the patients underwent neurosurgical treatment. The indication for surgery in 56.4 % (n=31) of the patients was instability in the spinal motion segment (SMS). Both one-stage (anterior or posterior stabilization) and two-stage operations consisting of posterior and anterior approaches, including with the use of minimally invasive techniques (8 cases), were performed. In 23 patients, foreign body removal was performed, including by means of videoimage endoscopy (in 5 cases). On average, the wounded had an operation on the 5th day after the injury. At discharge, motor neurological improvement or complete recovery was seen in 21.1 % (n=16) of the patients, while motor disorders remained at the initial level in 78.9 % (n=60). Sensory disorders decreased in 13.1 % (n=10), while 84.2 % (n=64) showed no improvement in sensory level. There was a significant decrease in the intensity of the pain syndrome. However, the number of patients with neuropathic pain decreased slightly (41 patients among all the examined at discharge versus 42 at admission). The functions of the pelvic organs were restored in 8.25 % (n=7) of the patients. At the stage of treatment in the specialized center, 49 % (n=39) of the patients had complications in different organ systems. The mortality rate was 2.5 % (n=2).